The long-term goals of the proposed research are to study the transport properties of the blood-retinal barrier system utilizing both in vivo and in vitro techniques. The immediate projects involve the collection of data on the sugar transport system in isolated pigment epithelial (PE) cells for kinetic analysis. From this analysis a kinetic model will be determined, and carrier affinities for glucose (Km) and the maximum velocities (Vmax) will be estimated. From preliminary data, the transport of glucose in isolated PE cells appears to follow complex kinetics which may indicate the existence of more than one mechanism for glucose translocation across the PE cell membrane. The effects of transport and metabolic inhibitors on this transport system will be assessed as well as possible regulatory agents such as alpha and beta stimulators and cyclic nucleotide analogs. The apparent transport kinetics of isolated PE tissue mounted as a membrane in a chamber will also be studied. The affects of selected agents on the apparent kinetic parameters will be ascertained. In vivo studies on the blood-retinal barrier are planned. These employ a method utilized in studies of the blood-brain barrier in small animals. This technique is referred to as the "internal water standard method" and will permit the determination of the retinal uptake indices of different types of substrates. The retinal uptake indices can be utilized in obtaining apparent kinetic parameters of transport. It is proposed to establish retinal uptake indices of selected hexoses and amino acids and to determine the effects of pharmacological agents on the transport characteristics. In addition, the permeability of the blood-retinal barrier will be altered by chemicals and radiation to determine if selective permeability changes develop under some treatments.